Measurement and mapping of human brain neural activity is of interest in medicine, neuroscience and psychology. Prior techniques of noninvasively measuring and mapping neural activity in the brain, such as electroencephalography (EEG) and magnetoencephalography (MEG) have been used both as research tools and for clinical diagnosis. Indirect methods of imaging neural activity measure tissue metabolism with positron emission tomography (PET) and single photon emission computed tomography (SPECT), or via the hemodynamic response measured with functional magnetic resonance imaging (fMRI) and functional near infrared spectroscopy (fNIRS) neuroimaging.
A direct noninvasive approach to measuring neuronal activity is with electroencephalography (EEG), however it can be difficult to interpret the waveforms of signal versus time plotted at various electrode locations on a subject's skull that are produced by traditional electroencephalographs. Electroencephalography uses electrodes placed in contact with the scalp to detect electric voltages generated by large groups of firing neurons within the brain, and is of use in diagnosis of epilepsy and other disorders of the brain.
Another noninvasive approach to measuring neuronal activity is magnetoencephalography (MEG) that measures magnetic fields produced by the brain. Commercial magnetoencephalography machines that sense and map the minute magnetic fields associated with the electric voltages and currents generated by large groups of firing neurons within the brain, and construct a three-dimensional map of detected neural activity, are available from companies such as Elekta AB, Stockholm, Sweden. In addition to magnetoencephalographic magnetic fields, biomagnetic fields also include magnetic fields generated by muscular activity, including muscular activity of the heart and intestines.
The dominant functional neuroimaging modality today is fMRI using blood-oxygen-level-dependent (BOLD) contrast to reconstruct three-dimensional movies of brain activity.
fNIRS (functional Near Infrared Spectrometry) is an alternative method of measuring hemodynamic responses near the surface of the brain, and which does not require the intense magnetic field and massive, immobile, magnets of fMRI. Because fNIRS relies on reconstruction of scatterers and absorbers of infrared light penetrating the brain, fNIRS does not well resolve activity in deep structures.
The hemodynamic response measured by fNIRS and fMRI is a localized change in blood flow, blood volume, and blood oxygenation that is coupled to neural activity by the activity of astrocytes, neurotransmitter signaling, and metabolites in the tissue. This neurovascular coupling involves a complex interplay of neuron activity and spatiotemporal variations in metabolism, blood flow and blood oxygen level. These processes are functionally connected in neurovascular units of the brain, which are composed of integrated networks of neurons, astrocytes, and vascular smooth muscle cells.
Combined multimodal measurement of neural and hemodynamic responses is preferred for studies of central nervous system (CNS) diseases and investigations where neurovascular coupling is questioned Impaired neurovascular coupling is implicated in stroke, hypertension, epilepsy, brain tumors, Alzheimer's and Parkinson's diseases and is the subject of intense biomedical research on brain dynamics. The available noninvasive neuroimaging instruments measure only one physiological process, i.e., neural, metabolic, or hemodynamic. Studies on neurovascular coupling currently require simultaneous operation of two neuroimaging modalities and typically suffer from mismatched resolution, mismatched data rates, and noise interference between the measurement modalities, e.g., combined fMRI and EEG.
Noninvasive imaging of magnetic nanoparticles is another, related, health-related field of interest. The magnetic properties of iron-core nanoparticles have opened new avenues of targeted cancer therapy, where they are used to selectively heat and kill tumor cells. Effective technology for noninvasive, in vivo, detection and location of magnetic nanoparticles is essential to the development and implementation of this targeted cancer therapy.
Hyperthermia treatment of cancerous tumors can effectively cause cancer cell death through mechanisms of protein denaturation and/or rupture of the cellular membrane. The destroyed cancer cells are then removed by macrophages, causing the tumor to shrink.
It is critically important in hyperthermia therapy to specifically target the cancer cells with the heat deposition and to minimize harm to healthy and/or critical tissues. Targeted hyperthermia therapy typically relies on localizing an energy-absorbing agent within the tumor prior to application of energy to the region. A variety of specific nanoparticles have been designed for this purpose. One approach is to coat the nanoparticles with gold and then to deposit energy with laser light.
Another approach is to use nanoparticles having an iron or iron-oxide component. In embodiments, the iron or iron-oxide component may be a core, or shell surrounding a core of another material. The iron or iron-oxide component gives these nanoparticles a high level of magnetic susceptibility. Since nanoparticles having such an iron or iron-oxide component typically have other materials surrounding the iron or iron-oxide component—such as biocompatible coatings and/or tissue-binding antibodies or agents—these nanoparticles are referred to herein as iron-core nanoparticles. Alternating magnetic fields are then used to selectively heat the magnetic nanoparticles in the tumor.
The exteriors of nanoparticles can also be modified to contain cancer-binding molecules that can selectively bind cancer cells and thereby deliver nanoparticles to cancerous cells. Several cancer-specific antibodies that can be conjugated to nanoparticles have already been approved by the Food and Drug Administration (FDA) and are clinically used to treat tumors. Cancer types that can be targeted in this way currently include colorectal, non-small cell lung, breast, leukemia, gastrointestinal, myeloma, lymphoma, kidney, and liver. Nanoparticles have also been engineered to target atherosclerotic plaques—which are of importance in heart disease and stroke—and Alzheimer's plaques. Iron-core nanoparticles can be used to target an increasingly wide range of diseases. These targeting mechanisms impart enhanced magnetic susceptibility to the targeted tumor region, and can be used both for treatment and for tumor localization and identification.
The magnetic susceptibility property of iron-core nanoparticles can also be used in conjunction with bound disease-targeting molecules, such as antibodies, for the detection of the diseased tissue in disease diagnostics. For example, the increased magnetic susceptibility of tissue tagged with nanoparticles will alter the contrast of images taken with MRI, or dyes delivered by nanoparticles, could be used to obtain enhanced contrast with NIRS. Imaging of iron-core nanoparticle locations is also important when using targeted chemotherapy and targeted hyperthermia treatments because damage to vital tissues and structures could result if the particles are in the wrong location when activated with the external energy.
Another related field is labeling, and reading of labels, of materials and manufactured parts for the purposes of authentication, track and trace, and supply chain management.
The problem of counterfeit electronic parts is a major problem in the Department of Defense (DOD) supply chain, as well as commercial aviation and drug supplies.